BuIIIB (P03625) Protein Card

General Information
Name BuIIIB
Alternative name(s) Bu3B
Organism Conus bullatus
Organism region Indo-Pacific
Organism diet piscivorous
Protein Type Wild type
Protein precursor BuIIIB precursor (3715)
Notes 10 μM rapidly blocks A-fiber compound action potentials in mouse sciatic nerve but not C-fiber CAPs [Wilson,M.J., Zhang,M (2015)].

Classification
Conopeptide class conotoxin
Gene superfamily M superfamily
Cysteine framework III
Pharmacological family mu conotoxin

Sequence
VGERCCKNGKRGCGRWCRDHSRCC(nh2)
Modified residues
positionsymbolname
25nh2C-term amidation
Sequence evidence nucleic acid level
Average Mass 2763.18
Monoisotopic Mass 2761.16
Isoelectric Point 12.36
Extinction Coefficient [280nm] 5500.00

Activity

IC50: Voltage-Gated Sodium Channels

TargetOrganismIC50Ref
Nav1.5R. norvegicus9.0uM+/-1.5Wilson,M.J. et al. (2011)
Nav1.6M. musculus1.8uM+/-0.3Wilson,M.J. et al. (2011)
(With rat β1 subunit.)0.32 μM+/-0.07Wilson,M.J. et al. (2015)
R. norvegicus(With rat β1 subunit.)30.36 μM+/-10.8Wilson,M.J. et al. (2015)
Nav1.7R. norvegicus>10uMWilson,M.J. et al. (2011)
Nav1.8R. norvegicus>10uMWilson,M.J. et al. (2011)

Kd: Voltage-Gated Sodium Channels

TargetOrganismKdRef
Nav1.1R. norvegicus360nM+/-132Wilson,M.J. et al. (2011)
Nav1.2R. norvegicus13nM+/-4Wilson,M.J. et al. (2011)
Nav1.3R. norvegicus200nM+/-86Wilson,M.J. et al. (2011)
0.20 μM+/-0.02Green,B.R. et al. (2014)
Nav1.4R. norvegicus3.6nM+/-1.4Wilson,M.J. et al. (2011)
0.004 μM+/-0.001Green,B.R. et al. (2014)

Synthetic variants
BuIIIA[del1-4]CCKNGKRGCGRWCRDHSRCC(nh2)
BuIIIB[C13A,C24A]VGERCCKNGKRGAGRWCRDHSRCA(nh2)
BuIIIB[C5A,C17A]VGERACKNGKRGCGRWARDHSRCC(nh2)
BuIIIB[C5U,C13A,C17U,C24A]VGER(Sec)CKNGKRGAGRW(Sec)RDHSRCA(nh2)
BuIIIB[C5U,C6A,C17U,C23A]VGER(Sec)AKNGKRGCGRW(Sec)RDHSRAC(nh2)
BuIIIB[C5U,C6A,C17U,D19A,C23A]VGER(Sec)AKNGKRGCGRW(Sec)RAHSRAC(nh2)
BuIIIB[C5U,C6A,C17U,H20A,C23A]VGER(Sec)AKNGKRGCGRW(Sec)RDASRAC(nh2)
BuIIIB[C5U,C6A,C17U,R18A,C23A]VGER(Sec)AKNGKRGCGRW(Sec)ADHSRAC(nh2)
BuIIIB[C5U,C6A,C17U,R22A,C23A]VGER(Sec)AKNGKRGCGRW(Sec)RDHSAAC(nh2)
BuIIIB[C5U,C6A,C17U,S21A,C23A]VGER(Sec)AKNGKRGCGRW(Sec)RDHARAC(nh2)
BuIIIB[C5U,C6A,G12A,C17U,C23A]VGER(Sec)AKNGKRACGRW(Sec)RDHSRAC(nh2)
BuIIIB[C5U,C6A,G14A,C17U,C23A]VGER(Sec)AKNGKRGCARW(Sec)RDHSRAC(nh2)
BuIIIB[C5U,C6A,G9A,C17U,C23A]VGER(Sec)AKNAKRGCGRW(Sec)RDHSRAC(nh2)
BuIIIB[C5U,C6A,K10A,C17U,C23A]VGER(Sec)AKNGARGCGRW(Sec)RDHSRAC(nh2)
BuIIIB[C5U,C6A,K7A,C17U,C23A]VGER(Sec)AANGKRGCGRW(Sec)RDHSRAC(nh2)
BuIIIB[C5U,C6A,N8A,C17U,C23A]VGER(Sec)AKAGKRGCGRW(Sec)RDHSRAC(nh2)
BuIIIB[C5U,C6A,R11A,C17U,C23A]VGER(Sec)AKNGKAGCGRW(Sec)RDHSRAC(nh2)
BuIIIB[C5U,C6A,R15A,C17U,C23A]VGER(Sec)AKNGKRGCGAW(Sec)RDHSRAC(nh2)
BuIIIB[C5U,C6A,W16A,C17U,C23A]VGER(Sec)AKNGKRGCGRA(Sec)RDHSRAC(nh2)
BuIIIB[C6A,C23A]VGERCAKNGKRGCGRWCRDHSRAC(nh2)
BuIIIB[E3(Dab),C5U,C6A,C17U,C23A] VG(Dab)R(Sec)AKNGKRGCGRW(Sec)RDHSRAC(nh2)
BuIIIB[E3(Dap),C5U,C6A,C17U,C23A]VG(Dap)R(Sec)AKNGKRGCGRW(Sec)RDHSRAC(nh2)
BuIIIB[E3(Gla),C5U,C6A,C17U,C23A]VG(Gla)R(Sec)AKNGKRGCGRW(Sec)RDHSRAC(nh2)
BuIIIB[E3(Orn),C5U,C6A,C17U,C23A]VG(Orn)R(Sec)AKNGKRGCGRW(Sec)RDHSRAC(nh2)
BuIIIB[E3A,C5U,C6A,C17U,C23A]VGAR(Sec)AKNGKRGCGRW(Sec)RDHSRAC(nh2)
BuIIIB[E3A]VGARCCKNGKRGCGRWCRDHSRCC(nh2)
BuIIIB[E3H,C5U,C6A,C17U,C23A]VGHR(Sec)AKNGKRGCGRW(Sec)RDHSRAC(nh2)
BuIIIB[E3K,C5U,C6A,C17U,C23A]VGKR(Sec)AKNGKRGCGRW(Sec)RDHSRAC(nh2)
BuIIIB[E3R,C5U,C6A,C17U,C23A]VGRR(Sec)AKNGKRGCGRW(Sec)RDHSRAC(nh2)
BuIIIB[G2A,C5U,C6A,C17U,C23A]VAER(Sec)AKNGKRGCGRW(Sec)RDHSRAC(nh2)
BuIIIB[G2A]VAERCCKNGKRGCGRWCRDHSRCC(nh2)
BuIIIB[G2a]VaERCCKNGKRGCGRWCRDHSRCC(nh2)
BuIIIB[R4A,C5U,C6A,C17U,C23A]VGEA(Sec)AKNGKRGCGRW(Sec)RDHSRAC(nh2)
BuIIIB[R4A]VGEACCKNGKRGCGRWCRDHSRCC(nh2)
BuIIIB[V1A,C5U,C6A,C17U,C23A]AGER(Sec)AKNGKRGCGRW(Sec)RDHSRAC(nh2)
BuIIIB[V1A]AGERCCKNGKRGCGRWCRDHSRCC(nh2)

References
Holford,M., Zhang,M.M., Gowd,K.H., Azam,L., Green,B.R., Watkins,M., Ownby,J.P., Yoshikami,D., Bulaj,G. and Olivera,B.M. (2009) Pruning nature: Biodiversity-derived discovery of novel sodium channel blocking conotoxins from Conus bullatus. Toxicon 53:90-98
Wilson,M.J., Yoshikami,D., Azam,L., Gajewiak,J., Olivera,B.M., Bulaj,G. and Zhang,M.M. (2011) μ-Conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve. Proc. Natl. Acad. Sci. U.S.A. 108:10302-10307
Kuang,Z., Zhang,M.M., Gupta,K., Gajewiak,J., Gulyas,J., Balaram,P., Rivier,J.E., Olivera,B.M., Yoshikami,D., Bulaj,G. and Norton,R.S. (2013) Mammalian neuronal sodium channel blocker μ-conotoxin BuIIIB has a structured N-terminus that influences potency. ACS Chem. Biol. 8:1344-1351
Wilson,M.J., Zhang,M.M., Gajewiak,J., Azam,L., Rivier,J.E., Olivera,B.M. and Yoshikami,D. (2015) α- and β-subunit composition of voltage-gated sodium channels investigated with μ-conotoxins and the recently discovered μO§-conotoxin GVIIJ. J Neurophysiol 113:2289-2301
Green,B.R., Zhang,M.M., Chhabra,S., Robinson,S.D., Wilson,M.J., Redding,A., Olivera,B.M., Yoshikami,D., Bulaj,G. and Norton,R.S. (2014) Interactions of disulfide-deficient selenocysteine analogs of μ-conotoxin BuIIIB with the α-subunit of the voltage-gated sodium channel subtype 1.3. FEBS J. 281:2885-2898

Internal links
Protein Precursor BuIIIB precursor (3715)
Nucleic acids
Structure NMR solution structure of Mu-contoxin BuIIIB

External links
Ncbi 2LO9_A

Tools